Leukotriene D.sub.4 and C.sub.4 (LTD.sub.4 /LTC.sub.4) and leukotriene B.sub.4 (LTB.sub.4) are products of the arachidonic acid metabolic pathway. LTD.sub.4 and LTC.sub.4 are associated with smooth muscle contraction and contract guinea pig ileum, human and guinea pig bronchi and human pulmonary artery and vein. LTB.sub.4 is associated with neutrophil stimulation and is characterized by chemotaxis, aggregation and degranulation. LTB.sub.4 is believed to be an important mediator of inflammation. High levels of LTB.sub.4 are detected in rheumatoid arthritis, gout, psoriasis, and inflammatory bowel disease. Thus antagonists of LTB.sub.4 are useful in the therapy of such diseases.
Gastroenterology, 1985: 88:580-7 discusses the role of arachidonic acid metabolites in inflammatory bowel disease.
British Medical Bulletin, (1983), vol. 39, No. 3, pp. 249-254, generally discusses the pharmacology and pathophysiology of leukotriene B4.
Biochemical and Biophysical Research Communications, Vol. 138, No. 2 (1986), pp. 540-546 discusses the pharmacology of a specific LTB.sub.4 antagonist which has a different structure than compounds of this invention.
The Journal of Medicinal Chemistry, 1977, Vol. 20 (3): 376 discloses a compound similar to the compounds of Formula I.
The prior art generally describes the above compounds as LTD.sub.4 antagonists for use as anti-allergy compounds or as antagonists of SRS-A, the slow reacting substance of anaphylaxis. In sharp contrast, compounds of Formula I are selective LTB.sub.4 antagonists useful treating inflammatory diseases.
U.S. Pat. Nos. 4,281,008, 3,822,148, and 4,006,245 generically disclose formulae which encompass compounds similar to Formula I but do not exemplify or otherwise enable the preparation and use of such compounds, nor do they teach the selective LTB.sub.4 antagonist activity of compounds of the present invention.
U.S. Pat. No. 4,889,871 generically discloses formulae which encompass the compound 1 described in Scheme 1 herein and which is used as an intermediate in the preparation of the compounds of this invention. The compounds are disclosed as useful anti-inflammatory agents.